Manufacture of 3,4-xylidine



Patnted Apr. 10, 1945 Viktor Weinmayr, mm... N. 3., minor to E. 1.

du Pont de Nemours & Company, n, Del., a corporation of Delaware NoDrawing. Application April 21, 1942,

Serial No. 439,938

3 Claims. (Cl. 260-580) This invention relates to preparation of 3,4-xylidine.

An object of this invention is to prepare new chemical compounds thatare useful as intermediates in the preparation of dyestuiis andlactofiavin. A further object is to provide new and improved processesfor preparing 3,4-xylidine.'

Other objects will appear hereinafter.

These objects are accomplished by the following invention.2-methyl-5-nitrobenzyl alcohol is made by hydrolyzing2-methyl-5-nitrobenzyl chloride. The carboxylic acid esters of 2-methyl-5-nitrobenzy1 alcohol are made by reacting 2- methyI-B-nitrobenzylchloride with a metal salt of a carboxylic acid. 2-methyl-5-aminobenzylalcohol and its carboxylic acid esters are made by suitably reducing2-methyl-5-nitrobenzyl alcohol and its carboxylic acid esters.3,4-xylidine is made by fully reducing 2-methyl-. 5-nitrobenzzylalcohol, 2-methyl-5-aminobenzyl alcohol or one of the carboxylic acidesters of these two benzyl alcohols.

The new intermediates prepared in accordance with this invention arerepresented by the following formula:

-on,on

1 May 21, 1943.

The invention is illustrated but not limited by the following examplesin which the parts are given by weight.

Example I 2-methyl-5-nitrobenzyl alcohoL-One hundred and seven parts ofanhydrous sodium carbonate and 289 parts of crystallized sodium acetateare dissolved in 1305 parts of 50% ethyl alcohol, and 290 parts ofdistilled 2-methyl-5-nit-robenzyl chloride (F. P. 59.6 C.) are added.The charge is maintained at a reflux temperature of about 85 C. forhours. The alcohol is then removed by distillation and the charge isheated until it reaches a temperature of 105 C. The reaction productseparates as an oil and solidifles to crystalline aggregates when cooledunder agitation. Two hundred and fifty parts of 2- methyl-5-nitrobenzylalcohol are isolated by filtration. This corresponds to a yield of 95.8%of theory based on 2-methyl-5-nitrobenzyl chloride. The crude productmelts from lit-75 C. Pure 2-methyl-5-nitrobenzyl alcohol melting at 77C. is obtained when the crude product is crystallized from 3 parts ofbenzene and 0.5 part of petroleum ether.

Example ll 2 lized sodium acetate in 400 parts of water. 2-

methyl-E-nitrobenzyl acetate separates as an oil. It is washed with warmwater to remove most of the sodium chloride and the excess 'of sodiumacetate and then distilled under reduced pressure. Two hundred and fortyparts of 2-methy1-5-nitrobenzyl acetate are obtained corresponding to ayield of 85.2% of theory. The product distills at nit- C. at 0.5 mm.pressure and has a freezing point of 483 C.

Example III Z-methyl-S-m'trobenzyL benzoete-One hundred and eleven partsof distilled 2-methyl-5- nitrobenzyl chloride (F. P. 59.6 C.) are heatedto the boil (106 C.) for 24 hours in a solution of 258 parts of sodiumbenzoate in 750 parts of water. 2-methyl-5-nitrobenzyl benzoate isformed and separates as a white crystalline product while the reactionmass i still near the reflux temperature.

I 160 parts of 2-methyl-5-nitrobenzyl benzoate,

equal to a yieldof 98.8%. of theory are obtained. The product melts at117-1l8 C. When crystallized from 15 parts of ethanol, it has a meltingp int of 118-1185 C.

Example IV Example V 2-methyl-5-aminobenzyl alcohol. Fifty-five tolueneare heated to 97-100 C. Two hundred and seven-tenths parts 'of distilled2-methyl-5- nitrobenzyl chloride (F. P. 59.6 C.), 58.5 parts ofpotassium acetate, and 200 parts of methanol are heated in an autoclaveto 125 C. for. 4 hours. After cooling to about 50 (Z 55.7 parts ofanhydrous sodium sulfate and 10 parts of nickel catalyst are added. Thereaction mass is heated under a pressure of 1000 pounds of hydrogen,first to 100 C. until the absorption has practically stopped and then to150 C. for two hours under the same hydrogen pressure. The nickelcatalyst is removed by filtration and the alcoholic solution isdistilled. Forty parts of 2-methyl-5- aminobenzyl alcohol are obtaineddistilling at 140 C. under a pressure of 0.5 mm. This product melts from105-109 C. and can be purified by crystallization to a melting pointof-111 C. The yield corresponds to 07.4% of theory based on 2-methyl-S-nitrobenzyl chloride.

Example VI z-methyl-fi-aminobenzyl acetate-Two hundred parts of2-methy1-5-nitrobe'nzyl acetate, 350

parts of thiophene-free benzene, 120 parts of magnesium oxide, and 10parts of nickel catalyst are heated to l0--80 C. under a pressure of 500pounds of hydrogen until no further absorption take place. About 2 hoursare required for the reduction. The benzene solution is filtered fromthe catalyst and distilled. One hundred and thirty-eight parts of2-methyl-5-aminobenzyl acetate are obtained distilling at 160-455 C. ata pressure of 0.5 mm. The product forms a yellow oil and is completelysoluble in dilute acids. The 5 yield corresponds to 80.5% of theory.

Example VII 3,4 :rylidine from 2 methyl 5 nitrobenzyl acetate-Onehiindred parts of Z-methyI-S-nitrobenzyl acetate (F. P. 48.8 C.) 500parts of thiophene-free benzene, 20 parts of nickel catalyst and 17parts of magnesium oxide are heated under a pressure of 500 pounds ofhydrogen, first to 70-90 C. until the absorption of hydrogen haspractically stopped, and then to 145-150 C. until there is no morehydrogen absorption for several hours. The time required for thereductionis about 6 hours. The benzene solution is separated from thecatalyst and distilled. Forty-five parts of 3,4-xylidine are obtained,distilling from 128-130" C. at a pressure of 35 mm. This corresponds toa yield of 77.7% of theory. The distilled product has a freezing pointfrom 47.5-4.8-.1 C. The purity of the compound can be increased by acrystallization from gasoline. The crystallized 3,4-xylidine has afreezing point of 49.1 C. 3,4-xylidine may be obtained in a similarmanner from 2-methyl-5-nitrobenzyl benzoate.

Example VIII 3.4-;cylidine from 2-methyl-5-aminobenzylalcohol-Twenty-seven and four-tenths parts of 2-methyl-5-aminobenzylalcohol (M. P. 111 0.), 21 parts of metallic sodium, and 50 parts of andfive parts of anhydrous isopropanol are added at such a rate that avigorous refluxing is main-.- tained. The reflux temperature is about 97C.

and about 2 hours are required to add the isopropanel. Refluxing iscontinued for about 2 hours after the addition of the 15017111 81101 isfinished. The charge is then diluted with about 500 parts of water andmost of the isopropanol is removed by distillation. The 3,4-xylidinewhich separated is taken up in benzene, washed with cold water anddistilled. Twenty-one parts of 3,4-xylidine are obtained having afreezing point of 48.1 C. The yield of 3,4-xylidine corresponds to 86.8%of theory.

Example IX 3,4 krylidine from 2 methyl 5 nitrobenzyl chloride.0nehundred and thirty-nine parts of distilled 2-methyl-5-nitrobenzylchloride, 360

parts of thiophene-free benzene, and 98 parts of anhydrous potassiumacetate are heated to 150 C. for two hours under a pressure of about 100pounds of nitrogen. After cooling to 50 0., 20 parts of magnesium oxideand 40 parts of nickel catalyst are added. The charge is heated to 65-70C. under a pressure of 800 pounds of hydrogen until no further hydrogenabsorption takes place, which will be the case after about three hours.Heating is then continued under the same hydrogen pressure until atemperature oi 150 C. is reached in four hours. The charge is maintainedat 150 C. under a pressure of 800 pounds of hydrogen for two hours, thencooled and filtered to remove the catalyst. 3,4-xylidine having afreezing point of 48 C. is obtained in good yield upon distillation.

There are a number of variations possible without departing from thespirit of the invention.

The hydrolysis of the 2-methyl-5-nitrobenzyl chloride to2-methyl-5-nitrobenzyl alcohol can be accomplished in the absence ofsodium acetate and alcohol, using aqueous sodium carbonate alone. Otheresters than the acetateor benzoate can be prepared and reduced.

Other catalysts than nickel, such as chromite catalysts or palladium canbe used for the reduction of the nitro bodies. Using a nickel catalyst,a reduction temperature below C. but above 40 C. is required to reducethe nitro group, using a hydrogen pressure of 400 to 1000 pounds. Thereduction of the ester group to the methyl group requires temperaturesabove 80 0., preferably to C. at a pressure of 400 to'1000 pounds ofhydrogen. Reduction temperatures as high as 290 C. will givesatisfactory 3,4-xylidine. After the reduction has once started thehydrogen pressure should be maintained fairly constant'*'to avoidformation or tarry by-products.

2-methyl-5-aminobenzyl alcohol can also be reduced with potassium inplace of sodium. Ethanol can be used in place of isopropanol, andtoluene may be left out.

It is not necessary to employ the various intermediates in their pureform or even to isolate them to obtain 3,4-xylidine.- Without changingthe quality of 3, 4-xylidine, crude 2-methyl-5-nitrobenzyl alcohol orcrude 2-methyl-5-nitrobenzyl acetate may be reduced to give 3,4-xylidineof a freezing point 47.5-48.1" 0., requiring no purification other thandistillation from the reaction mass. Z-methyI-S-aminobenzyl alcohol canbe made from 2-methyl-5-nitrobenzyl chloride directly without isolationof 2-methyl-5-nitrobenzyl alcohol. Similarly 3,4-xylidine can be madefrom 2-methyl-5-nitrobenzyl chloride directly without isolating2-methyl-5-nitrobenzyl acetate.

Isomers of 2-methyl-5-aminobenzyl alcohol are valueless for thepreparation of 3,4-xylidine.

Resort may be had to such modifications and variations as fall withinthe spirit of the invention and the scope of the appended claims.

I claim:

1. A process of making 3,4-xylidine which comprises catalyticallyhydrogenating 2-methyI-5- nitrobenzyl acetate, said hydrogenation beingcontinued until-the nitro group of said compound is converted to anamino group and the -CH2OCO- CH3 side chain of said compound is reducedto a methyl group.

2. A process of making 3,4-xylidine which comprises catalyticallyhydrogenating 2-methyl-5- nitrobenzyl benzoate, said hydrogenation beingcontinued until the nitro group of said compound is converted to anamino group and the -CH2OCO CsHs side chain of said compound is reducedto a methyl group.

3. A process of making 3,4-xy1idine which comprises catalyticallyhydrogenating a carboxylic acid ester of 2-methyl-5-nitrobenzyl alcohol,said ester having the general formula 02 wherein R is a member of theclass consisting of aliphatic and aromatic hydrocarbon groups, saidhydrogenation being continued until the nitro I group of said compoundis converted to an amino group and the 0 H10 fi-R

